Research

June 2008: The Immune Basis of Liver Disease - A BSG Research Workshop

A workshop on liver immunology was held at the University of Birmingham on 9th and 10th June 2008 organised by David Adams on behalf of the Research Committee.

 

The aim was to produce an interactive workshop covering basic immunology related to the liver through to animal models of liver disease and human disease pathogenesis. On these terms all agreed the workshop was a success with vigorous discussion and several new collaborations formed during the two days. After a thought-provoking introduction from Cliona O’Farrelly covering the evolution of the hepatic immune system and how our concepts of liver immunology have changed over the last decade the first session covered aspects of innate immunity. The role of intrahepatic γδ T cells in regulating immune responses to pathogens was covered by Simon Carding and Salim Khakoo outlined the role of NK cells in liver injury and in hepatitis C infection. Andy Stagg provided an update on human dendritic cell biology and the critical role played by the microenvironment and microflora in shaping immune responses and John Iredale reported the complex roles played by macrophages in liver inflammation both in driving liver damage and promoting tissue repair. David Adams suggested that fibroblasts regulate lymphocyte recruitment to the liver thereby directly linking fibrosis and inflammation. The first session of the second day focussed on antigen presentation in the liver. Percy Knolle presented new data on the ability of sinsuoidal endothelial cells and hepatocytes to induce immune tolerance and the role of specific molecules such as B7-H1 in these processes and Angus Thomson discussed the nature and function of intrahepatic dendritic cells and the role played by pathogens, cytokines and adapter molecules such as DAP-12 and STAT-3 in their maturation and function. Wing-Kin Syn presented novel data on the role of the hedgehog pathway in regulating liver regeneration through effects on NKT cell activation and function and Bertus Eksteen discussed links between the mucosal immune system and the liver and how dysregulation of this can lead to uncontrolled inflammation in the liver.

Paul Klenerman started a session on viral hepatitis by reporting that the phenotype of antigen-specific T cell may predict outcome in hepatitis C infection; he described a novel subset of HCV-associated lymphocytes that express CD161 and the chemokine receptor CXCR6. Dermot Kelleher described immune escape in the Irish cohort of HCV-infected mothers and then went onto to show how HCV viral proteins can modulate lymphocyte migration through PKCβ mediated effects on integrin activation and chemokine secretion. Mala Maini reported that Bim can mediate the deletion of antigen-specific T cells in patients who fail to clear HBV and that a lack of arginine leads to low levels of TCRζ after T cell activation and a failed effector response.

In a session covering disease pathogenesis Mark Thurz reported that polymorphisms and SNPs in immune associated genes may contribute to the outcome of viral hepatitis and that mutations in genes associated with coagulation are associated with accelerated fibrosis. Diego Vergani reviewed current understanding of autoantigens in autoimmune hepatitis and showed how defective regulatory T cell function contributes to disease development. David Jones reviewed autoantigens and trigger factors in PBC and presented data on novel animal models that may elucidate pathogenesis. Giesa Tiegs discussed the pathogenesis of liver injury in murine concanavalin hepatitis and showed how the balance between regulatory and effector pathways is critical in determining outcome. John Kirby discussed how TGFβ and SMAD signalling can drive inflammation-induced fibrogenesis by the process of epithelial to mesenchymal transition. Finally Kevin Maloy presented exciting new data on the interactions between the Th17 associated cytokines IL22 and IL23 and the generation of regulatory T cells and Th17 inflammation.

All agreed that the workshop had been a success and that the informal and interactive nature had been highly conducive in promoting new collaborations and in allowing trainees to interact with leaders in the field. There was a strong opinion that this format should be repeated in the future.

Professor David Adams